vinflunine exerts the cytostatic effects associated with the inhibition of tubulin polymerization during cell mitosis.
vinflunine exhibits linear pharmacokinetics when administered at standard doses (from 30 mg / m2 to 400 mg / m2).
Exposure vinflunine blood – AUC was significantly correlated with severity of leucopenia, neytropeiii and the severity of the patient’s asthenia
vinflunine moderately bound to plasma proteins (67,2 ± 1,1%), the ratio between plasma concentration and total blood volume is 0.8 ± 0.12. Communication with the proteins is carried out mainly with linoproteinami high density and serum albumin does not reach saturation in the range of therapeutic concentrations of the drug. The interaction with the alpha-1-acid glycoprotein and platelet immaterial (
The maximum volume of distribution is 2422 ± 676 liters (about 35 liters / kg), confirming a broad distribution of the drug in the tissues.
The main active metabolite in the blood is a 4-O-deatsetilvinflunin resulting from the action of various esterases. All other identified metabolites are formed under the influence of isoenzyme cytochrome CYP3A4.
T1 / 2 is 40 h ditartrate.
The formation and excretion of the metabolite 4-O-deatsetilvinflunina slower it T1 / 2 is about 120 hours. Isolation of vinflunine and its metabolites occurs in the faeces (2/3) and urine (1/3).
Pierre Fabre medicament France
Active substance: 25 mg of vinflunine
monotherapy in adult patients with advanced or metastatic urothelial transitional cell carcinoma after therapy with platinum, which has not yielded positive results.
- hypersensitivity to the active substance or to vinca alkaloids;
- infectious disease within 2 weeks before the start of therapy;
- absolute neutrophil count of less than 1,500 cells / .mu.l of blood during the first administration of the drug and less than 1,000 cells / ml of blood for subsequent administration of the preparation or platelets less than 100,000 cells / ml of blood;
- Pregnancy and breast-feeding;
- Children under 18 years of age.
- Syndrome congenital long interval Q-T, cardiac diseases (cardiac insufficiency, myocardial infarction, bradycardia).
- electrolyte imbalance (e.g., hypokalemia, hypomagnesemia).
- Simultaneous reception medicaments interval prolonging Q-T (including antiarrhythmic IA and Class III).
- Liver failure secondary to severe (Zhavlor standard dose of the drug should be reduced).
- Renal failure secondary to severe (Zhavlor standard dose of the drug should be reduced).
- Age older than 75 years (recommended standard dose Zhavlor should be reduced).
Infectious and parasitic diseases: often – infections of neutropenia, infectious complications (viral, bacterial, fungal); infrequently – bacterial sepsis of neutropenia
Violations of the blood and lymphatic system: very often – neutropenia, leukopenia, anemia, thrombocytopenia; often – febrile neutropenia
Violations of the immune system: often – hypersensitivity
Abuses by metabolism: often – anorexia; often – dehydration
Mental Disorders: often – insomnia
Disorders of the nervous system: very often – peripheral sensory neuropathy; often – fainting, headache, dizziness, neuralgia, a violation vkusovospriyatiya, neuropathy; rarely – peripheral motor neuropathy
Violations of the organ of vision: rarely – a violation of visual perception
Violations of the organ of hearing and labyrinth disorders: often – pain in the ear; rarely – dizziness, feeling of tinnitus
Abuses by heart: often – tachycardia; infrequently – myocardial ischemia, myocardial infarction
Abuses by vessels: often – arterial hypertension, venous thrombosis, arterial hypotension
Disorders of the respiratory system side, chest and mediastinal disorders: often – shortness of breath, cough; rarely – acute respiratory distress syndrome, pain in the larynx and pharynx
Disorders of the gastrointestinal tract: often – constipation, abdominal pain, nausea, vomiting, stomatitis, diarrhea; often – ileus, dysphagia, disorders of oral mucosa, dyspepsia; rarely – pain when swallowing, gastritis, esophagitis, gingivitis
Disorders of the skin and subcutaneous tissue disorders: very often – alopecia; often – skin reactions (rash, urticaria), itching, rash; rarely – erythema, dryness of the skin
Violations of the musculoskeletal system and connective tissue: very often – myalgia; often – muscle weakness, arthralgia, musculoskeletal pain of different localization, including chest pain, pain in the back, jaw, in the extremities
Violations of the kidney and urinary tract: rarely – renal failure
General disorders and at the injection site: very often – asthenia, fatigue, injection site reactions, fever; often – chest pain, fever, pain and / or swelling at the injection site; infrequently – extravasation
Laboratory and instrumental data: very often – weight loss; Infrequent – increased transaminases activity, weight gain
How to accept, acceptance rate and dosage
The recommended dose is 320 mg / m2vinflunina a twenty-minute intravenous infuzin 1 every 3 weeks.
In the dark place at a temperature of 2-8 ° C
In a joint application of vinflunine with cisplatin, carboplatin, capecitabine, doxorubicin or gemcitabine were observed pharmacokinetic drug interactions.
The combined use of ketoconazole (at a dose of 400 mg orally 1 every 8 days) increases ditartrate blood exposure (30%) and to increase the exposure of its metabolite 4-O-deacetyl-ditartrate (50%).
Avoid joint application of vinflunine and potential inhibitors isoenzyme CYP3A4 (ritonavir, ketoconazole, itraconazole, grapefruit juice) or inducers (rifampicin, grass zveroboyaprodyryavlennogo), as these substances can vary the concentration of vinflunine.
combined use should be avoided with drugs prolong the interval Q-T / Q-Tc.
The combined use of opioids increases the risk of constipation.
The possible interaction with vinflunine paclitaxel and docetaxel (CYP3 substrates) was studied in the in vitro study (slight inhibition of vinflunine metabolism), but special clinical studies on the interaction of these drugs is not performed.
The drug Zhavlor intended solely for intravenous administration.
Intrathecal administration leads to death, is strictly forbidden!
Treatment with Zhavlor should be carried out under the supervision of a physician who has experience with anticancer drugs.
The therapy carried out under strict hematological control, determining the number of leukocytes, neutrophils, platelets and hemoglobin concentration before each next infusion.
In order to prevent constipation, the first to fifth or seventh day after each application of the preparation to be applied Zhavlor laxatives, as well as fiber-rich diet and drinking liquids.
With the introduction of the drug through a peripheral vein, vinflunine can induce her phlebitis.
Men and women should use reliable methods of contraception during treatment and three months after the end of therapy.
Due to the possibility of irreversible loss of fertility resulting from treatment ditartrate, patients should be given a recommendation of sperm preservation before the course of treatment Zhavlor.
The efficacy and safety of the drug are not defined for patients equal to or more than 2 functional class.
General precautions for preparation and application.
The preparation and implementation of the solution produces medical personnel properly trained in handling cytotoxic agents.
All of the preparation of the solution for infusion procedures require aseptic conditions. Medical staff recommended to use gloves, goggles and protective clothing.
If the product enters solution with the skin or mucous membranes must be immediately and thoroughly wash them with soap and water.
Pregnant women are forbidden to work with the drug Zhavlor.
The drug Zhavlor intended for single use only.
All unused material and waste should be disposed of in accordance with the requirements for the handling of tsitotoksichsskimi drugs.
The effect on the ability to drive vehicles and management mechanisms
Advanced Studies on the effect of the drug on the ability to drive vehicles and management mechanisms are not carried out. However, patients are not recommended to drive and engage in other potentially hazardous activities that require high concentration and psychomotor speed reactions, if they experience adverse reactions may affect the performance of these activities (eg dizziness, fainting).